CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis

Masanori A. Murayama, Shigeru Kakuta, Asuka Inoue, Naoto Umeda, Tomo Yonezawa, Takumi Maruhashi, Koichiro Tateishi, Harumichi Ishigame, Rikio Yabe, Satoshi Ikeda, Akimasa Seno, Hsi-Hua Chi, Yuriko Hashiguchi, Riho Kurata, Takuya Tada, Sachiko Kubo, Nozomi Sato, Yang Liu, Masahira Hattori, Shinobu Saijo, Misao Matsushita, Teizo Fujita, Takayuki Sumida and Yoichiro Iwakura ()
Additional contact information
Masanori A. Murayama: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Shigeru Kakuta: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Asuka Inoue: Faculty of Medicine, University of Tsukuba
Naoto Umeda: Faculty of Medicine, University of Tsukuba
Tomo Yonezawa: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Takumi Maruhashi: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Koichiro Tateishi: Tokai University
Harumichi Ishigame: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Rikio Yabe: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Satoshi Ikeda: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Akimasa Seno: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Hsi-Hua Chi: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Yuriko Hashiguchi: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Riho Kurata: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Takuya Tada: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Sachiko Kubo: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science
Nozomi Sato: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Yang Liu: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Masahira Hattori: Graduate School of Frontier Sciences, The University of Tokyo
Shinobu Saijo: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Misao Matsushita: Tokai University
Teizo Fujita: Fukushima Prefectural General Hygiene Institute
Takayuki Sumida: Faculty of Medicine, University of Tsukuba
Yoichiro Iwakura: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6−/− mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6−/− mice and C1qtnf6−/− embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases.

Date: 2015
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DOI: 10.1038/ncomms9483

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